Prostate cancer [PC] is the most frequently diagnosed malignancy in men and the second leading cause of cancer death. In this Phase I SBIR proposal, we will develop a novel radioIodinated [I-131] ProDrug [131IPD] that has been designed to be specifically hydrolyzed within primary and metastatic well differentiated and poorly differentiated PC lesion into radioiodinated Drugs [*ID] that are trapped within these tumors. SPECIFIC AIMS: (1) Synthesize and characterize 127IPD/125IPD derivative and corresponding 127IDs/125IDs; (2) inject 125IPD into PC-bearing mice, determine tumor uptake and tumor-to-normal tissue ratios over time, and estimate the doses deposited in the tumor and normal tissues; and (3) synthesize 131IPD derivative, identify its MTD in mice, and confirm therapeutic efficacy in PC-bearing mice. We anticipate that these studies will identify a novel and commercially viable 131IPD that will deposit therapeutically effective [i.e., curative] radiation doses specifically within PC lesions and that this radiopharmaceutical ? post future Phase II SBIR funding and VC-funded clinical trials ? will (i) enable the coupling of imaging [123IPD] and treatment [131IPD] and therefore the personalization of treatment, (ii) move meaningful intervention to an earlier point and forestall the development of metastatic disease, and (iii) diminish/eliminate the death of patients with this devastating disease.